Scar formation after a surgical procedure or injury is unpredictable and both physicians and patients are highly concerned with minimizing scar appearance. In spite of availability of various in vivo and in vitro studies, limited information is available on the exact cause of scarring. Scaring can lead to the formation of raised nodules called keloids. Scars can also be raised and erythematous in which case they are called hypertrophic scars. Other manifestations of scarring include the formation of adhesions after surgery, frozen shoulder syndrome (from adhesive capsulitis) and acne vulgaris.
Hypertrophic scar formation is often a result of an overproduction and excess deposition of collagen by fibroblasts caused by an increased or prolonged activity of TGF-β1. The surface of the keloid could be smooth, but in most of the cases, it is observed that the keloids are nodular or ridged. This is due to the presence of thickened and hyalinized collagen fibrils, mostly type I and III, which are randomly oriented in case of Keloids. Collagen synthesis in keloids is 3 times greater than in hypertrophic scars and 20 times greater than in normal skin. Adhesive capsulitis is characterized by collagenous tissue associated with fibroblasts and myofibroblasts.
Current treatments for hypertrophic scars and keloids include pressure therapy, silicone based products, radiation therapy, corticosteroid application, cryosurgery and laser surgery. All the above listed treatment options have to be continued over an extended course of time and are expensive and some others pose radiation risks. These treatment modalities are not a permanent cure, and there is a high incidence of recurrence of keloids, with the recurrence rate being reported from 45-100%.
Most therapeutic approaches remain clinically unsatisfactory due to lack of understanding of the physiological processes involved in wound healing and excessive scarring. Currently no successful clinical treatment is available to healthcare providers and patients for conditions with excessive production of collagen. In addition, systemic side effects are high for current treatment options.
Though a number of the treatment strategies have been tried, none of the current treatments are long acting in duration. Use of protease enzymes, including collagenase, papain and elastase as solutions has been reported previously. These systems do not work effectively because the protease activity is self-limiting and is effective for a few hours to 1-2 days only. This is primarily due to the fact that protease enzymes in solution are rapidly degraded by their own activity since all of these enzymes are proteins and hence capable of self-degradation. In addition, once a protease enzyme is in solution form, it is subject to chemical degradation from reactions such as hydrolysis which also results in rapid loss of activity. When protease solutions are injected in the body, the protease are quickly absorbed through the blood or lymph capillaries and removed from the area of injection. This further reduces the amount of protease available at the site of action. Therefore, unless the composition is injected repeatedly over a period of several weeks, the therapy does not work. Since the treatment of scars requires a treatment lasting several weeks or months, there exists a need for a treatment method that does not involve repeated applications or injections of the medicament.